tbuckley/cabot-search huggingface dataset:
LUNG cancer: Supportive oncology program development for patients and care partners: A qualitative study.
Authors: Dori Michelle Beeler, Kathryn Finch Mileham, Beth York, Michele Szafranski, Declan Walsh
Journal: Journal of Clinical Oncology (2022)

e18652 Background: Lung cancer patients (LCP) have various unmet needs. Evidence supports tailored services to provide individuals information and interaction with healthcare professionals (HCP). We conducted a qualitative study of the ideal supportive care services and structure for LCP and care partners (CP) within Levine Cancer Institute, a regional, multi-site cancer system. Methods: Methods included Focus Groups (FG) and a paper-based survey (PBS) in the Section of Thoracic Oncology. FG included HCP, local Lung Cancer Support Group leadership, LCP, and their CP. FG identified important topics for LCP, CP, and HCP. FG recordings were transcribed, analyzed, and incorporated with the evidence base to inform PBS development. LCP and CP participated in the PBS and responses analyzed with REDCap (v11.1 11, ©2022 Vanderbilt). FG and PBS data were compared for overlap and discordance. Results: FG (total N = 18) identified four Themes: 1) unmet needs 2) program structure 3) barriers to care 4) program content; each analyzed further into three codes (Table). FG Themes are presented in order of frequency (FQ) of unique comments. Unmet needs (FQ=25) included: loneliness, care for the CP, onboarding burden. Structure (FQ=24) included: innovation, variability, virtual. Barriers to care (FQ=20) included: seeking/needing knowledge, transportation, psychosocial. Content (FQ=18) included: combined content and services, financial, educational. Among the responses (total n = 44), strong overlap existed in six PBS areas. Most agreed on seeking/needing knowledge and psychosocial barriers. The majority agreed with combined content and services and the importance of financial and educational content. Variability was specified by agreement on printed and patient portal digital materials with a moderate preference for virtual meetings. Discordance was found across loneliness and transportation while care for the CP, onboarding burden, and innovation were neutral or irrelevant. Conclusions: FG findings confirmed unmet needs, program structure, barriers to care, and program content as integral LCP and CP program concerns. Identified overlap between these Themes and PBS responses are addressed in the ideal LCP and CP support program. This methodology can be generalized to guide future program development to serve other populations and cancer institutes. [Table: see text]
State public welfare spending and racial/ethnic disparities in overall survival among adults with cancer.
Authors: Justin Michael Barnes, Kenton J Johnston, Nosayaba Osazuwa-Peters
Journal: Journal of Clinical Oncology (2022)

6509 Background: State public welfare spending may partially address social determinants of health and mitigate structural racism. However, its association with racial and ethnic disparities and overall survival for newly diagnosed patients with cancer is unknown. Methods: Adults ages 18 and older with a new cancer diagnosis from 2007-2016 were queried from the Surveillance, Epidemiology, and End Results program. Annual state spending data were obtained from the US Census Bureau. We evaluated the association of 5-year overall survival (OS) and public welfare spending using cluster-robust regression. Analyses were conducted overall, by race and ethnicity, and by cancer site. To determine whether public welfare spending was associated with changes in racial and ethnic disparities in survival, we additionally assessed for interaction effects between public welfare spending and race and ethnicity. Analyses were adjusted for covariates including age, sex, metropolitan residence, state, county-level income and education, insurance status, cancer site, stage at diagnosis, and year of diagnosis. Sensitivity analyses were conducted also accounting for state Medicaid expansion effects and state spending on health care and hospitals. Results: A total of 2,925,550 individuals were identified in our cohort. 5-year OS was 10.6% lower in non-Hispanic Black vs. White patients. Public welfare spending was not associated with 5-year OS overall (0.25 % per 10% increase in spending, -1.47 to 1.96, p =.78) or for non-Hispanic White patients (0.52% per 10% increase in spending, 95% CI -1.30 to 2.33, p =.58). However, increased public welfare spending was associated with increased 5-year OS among non-Hispanic Black patients (2.02% per 10% increase in spending, 95% CI = 0.01 to 4.03, p =.049). There was a 4.46% (95% CI = 2.63 to 6.30, p interaction &lt;.001) narrowing of the 5-year OS disparity in non-Hispanic Black relative to White patients per 10% increase in spending, or a 42% closure of the 10.6% OS disparity. Specifically, increased public welfare spending was associated with a narrowed Black vs. White 5-year OS disparity for patients with breast (7.50% increase in 5-yr OS for non-Hispanic Black relative to White per 10% increasing in spending, corresponding to closing 42.1% of the disparity), cervical (12.2%, 45.9%), colorectal (3.37%, 44.9%), head and neck (8.23%, 35.7%), liver (4.54%, 44.8%), lung (1.76%, 63.3%), ovarian (6.43%, 35.9%), prostate (2.89%, 41.9%), bladder (7.62%, 42.9%), and uterine cancers (14.9%, 40.9%). Results were similar after accounting for state health care and hospital spending and state Medicaid expansion effects. Conclusions: State investment in public welfare was associated with improved 5-year OS for non-Hispanic Black individuals with cancer, decreasing racial disparities in cancer outcomes overall and for many cancer sites.
Immune checkpoint inhibitor therapy increases systemic SDF-1, cardiac DAMPs Fibronectin-EDA, S100/Calgranulin, Galectine-3 and NLRP3-MyD88-chemokine pathways.
Authors: Vincenzo Quagliariello, Margherita Passariello, Annabella Di Mauro, Ciro Cipullo, Andrea Paccone, Alessandro Inno, Claudia De Lorenzo, Nicola Maurea
Journal: Journal of Clinical Oncology (2022)

e14516 Background: Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy for improving cancer therapy outcomes. However, several ICIs-induced side effects emerged in a fraction of these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. We studied the pro-inflammatory and pro-fibrotic effects of short-term ICIs therapy in preclinical models. Methods: C57/Bl6 mice were treated with Ipilimumab, Pembrolizumab or Nivolumab (15 mg/kg) through intraperitoneal injections for 10 days. Before (T0) and after treatments (T10), analysis of fractional shortening, ejection fraction, radial and longitudinal strain were performed through 2D-echocardiography (Vevo 2100, Visual Sonics Fujfilm). Fibrosis, necrosis, hypertrophy and vascular/myocardial NF-kB expression were analyzed through Immunohistochemistry (IHC) of treated cardiac tissues. Systemic levels of SDF-1, myocardial expression of DAMPs (Fibronectin-EDA, S100/Calgranulin, Galectine-3), NLRP3, MyD88 and twelve cytokines/growth factors have been analyzed. In parallel, in a human in vitro model, human cardiomyocytes co-cultured with hPBMC were exposed to ICIs (200 nM) for 72h. After treatment, production of DAMPs and 12 cytokines/growth factors were analyzed in the supernatant through colorimetric and enzymatic assays. Results: Radial and longitudinal strain were decreased after 10 days of ICIs therapy. Histological analysis of NF-kB expression shows that short-term anti-CTLA-4 or anti-PD-1 treatment increased vascular and myocardial inflammation. No myocardial hypertrophy was seen with the exception of the pembrolizumab group. Systemic SDF-1 was drastically increased after treatment with ICIs. Myocardial fibrosis and expression of galectin-3, pro-collagen 1-α and MMP-9 were increased after treatment with all ICIs. Both anti-CTLA-4 or anti-PD-1 treatments increased the expression of DAMPs, NLRP3 inflammasome and MyD88. Conclusions: This study demonstrates that therapy with anti-CTLA-4 and anti-PD-1 antibodies increases systemic SDF-1 and myocardial NLRP3, MyD88 and DAMPs expression in preclinical models. A significant secretion of pro-inflammatory cytokines in myocardial tissue was also induced after ICIs therapy. Significant histological changes were seen and strong vascular NF-kB expression was observed in all groups.
BTCRC-HN17-111, A phase 2 trial of ADT (goserelin) in combination with pembrolizumab for patients with advanced salivary gland tumors expressing androgen receptor (AR).
Authors: Manish Patel, Naomi Fujioka, Daniel Fellows Pease, Lawrence Eric Feldman, Francis P. Worden, Douglas Earl Laux, Yanis Boumber, Ranee Mehra, Emilian Racila, Qing Cao, Justine Yang Yang Bruce
Journal: Journal of Clinical Oncology (2022)

e18091 Background: Salivary gland cancers (SGC) are rare malignancies with no standard systemic therapy available for patients with recurrent or metastatic disease. Androgen receptors (AR) are expressed and functional on many SGCs. Preclinical data suggested possible synergy between ADT and immune checkpoint blockade. The Big Ten Cancer Research Consortium conducted an open label, multi-center, Simon’s two-stage, phase II trial using ADT in combination with pembrolizumab for advanced salivary gland tumors that express AR. Here, we report the preliminary results of the first stage of the trial. Methods: Patients with incurable recurrent or metastatic SGC (any histology) with at least 20% of tumor cells expressing AR by immunohistochemistry were recruited. Patients who had received prior ADT or immune checkpoint therapy were excluded. Patients were treated with subcutaneous injection of goserelin 3.6mg every 4 weeks. Pembrolizumab 200mg was administered intravenously every 3 weeks starting 14 days after initiation of goserelin. Disease assessment was performed after completion of 4 cycles of therapy. Primary endpoint was objective response rate. Key secondary endpoints included PFS, OS, and safety of the combination. Stopping rules for excess toxicity were employed. We planned enrollment of 9 patients in the initial stage, and plan to complete enrollment if we observed³ 2 objective responses. Results: Between June 2019 and June 2021, we enrolled 9 patients into the study to complete the first stage. 7/9 were men, 8/9 were white, and the median age was 67 years old. A total of 5 ductal carcinomas, 3 adenocarcinomas, and 1 adenoid cystic carcinoma patients were enrolled. Patients had a median of 1 prior line of treatment. No stopping boundaries were crossed for excess toxicity. One patient experienced Grade 4 Stevens-Johnsons syndrome requiring permanent discontinuation of pembrolizumab. Otherwise, there was no increase in immune-related toxicity from what might be expected with pembrolizumab alone. Objective responses were observed in 2/9 patients (22%). Both responses were seen in ductal carcinomas. The best response was partial response in 2/9, while 6/9 had stable disease as best response for clinical benefit rate of 88% (8/9). The 6-month PFS was 63% (CI 19-85%). Conclusions: The combination of goserelin and pembrolizumab was well-tolerated and show preliminary evidence of efficacy in the first stage of the trial. The second stage of the trial has opened to accrual with a plan to enroll 11 additional patients. Clinical trial information: NCT03942653.
A phase 1 study in patients with advanced non-small cell lung cancer treated with stereotactic radiotherapy to the primary tumor combined with durvalumab and tremelimumab.
Authors: Hanneke Kievit, M Benthe Muntinghe-Wagenaar, Fred Ubbels, Robin Wijsman, Lucie Hijmering-Kappelle, Birgitta Hiddinga, Harry J.M. Groen, Huib A.M. Kerstjens, Anthonie J. van der Wekken, T.Jeroen Jeroen Nicolaas Hiltermann
Journal: Journal of Clinical Oncology (2022)

e21121 Background: Cancers can be recognized by the immune system and immunotherapy (ICI) has become an important treatment for lung cancer. Compared to chemotherapy, combining an anti-CTLA-4 and PD-L1 inhibitor increases response- and survival rates independent of PD-L1 status. We hypothesized that adding stereotactic radiotherapy (SBRT) to increase the release of cancer cell antigens might improve treatment results even further. Because of accumulating tumor heterogeneity it may be important to irradiate the primary tumor (addressing trunk mutations), rather than its metastases (branch mutations). We assessed toxicity of adding SBRT to (dual) ICI. Methods: In 3 sequential cohorts, ICI regimes combined with SBRT were studied in stage IIIB/IV NSCLC patients progressing on chemotherapy. All patients were irradiated on an FDG avid part of the primary tumor (1x20 Gy on 9cc) 1 week after the 1 st dose of ICI; in case of dual ICI the 1 st dose of the 2 nd ICI was administered within 1 week following SBRT. Following treatments both ICI were combined. The 1 st cohort (n = 3) received durvalumab (D) monotherapy for up to 1 year. The 2 nd cohort starting with tremelimumab (T) and the 3 rd cohort starting with D (both n = 6) received a combination of D and T (4 cycles) followed by D monotherapy for up to 1 year. The 2 nd and 3 rd cohort only proceeded when dose limiting toxicities (DLT) occurred in ≤33% of cases in the previous cohort. DLT was defined as any grade ≥3 toxicity that occurred during the first 8 weeks of therapy. Treatment related adverse events (TRAEs) were categorized using NCI CTCAE version 4.3. Descriptive statistics were used to summarize baseline characteristics and TRAEs. Results: Fifteen patients were included from June 2018 to November 2020. Last study visit was in September 2021. Baseline characteristics of the groups were comparable. The median irradiated tumor volume was 9.13 cc (8.98-9.60 cc) with a mean lung dose of 0.44 Gy (0.14-0.73 Gy). The V20 was nihil (0-0.1%) and the V5 1.8% (0-4%). There was 1 DLT in cohort 3 (colitis grade 3). There was 1 low grade TRAE (pneumonitis grade 2) in cohort 1. In cohort 2, 6 low grade TRAEs (CTC 1-2) were observed and 2 high grade (CTC 3) in 1 patient, who discontinued treatment. In cohort 3, 4 low grade and 1 high grade TRAE occurred. Median progression free survival was 2 months, median overall survival 10 months. Conclusions: No additional toxicity was observed by adding SBRT to the primary tumor to (dual) ICI. Clinical trial information: 2017-002797-39. [Table: see text]
Surgical subtypes and survival in Ewing sarcoma: A National Cancer Database (NCDB) analysis.
Authors: Connor Tupper, Peter T. Silberstein, Vincent Eaton
Journal: Journal of Clinical Oncology (2022)

e23511 Background: Ewing sarcoma (EWS) is the one of the most common primary malignancies of bone, more commonly affecting the pediatric population Standard of care for EWS currently involves surgical intervention in combination with chemotherapy, in addition to the potential use of preoperative and/or postoperative radiation on a case by case basis. To date, there is not much in the literature reported regarding different surgical subtypes in these patients. Thus, this study aims to analyze survival outcomes amongst the different surgical subtypes in EWS patients. Methods: Using the NCDB, patients diagnosed with EWS between 2004-2018 were identified using ICD-O-3 histology code 9260. The cohort was analyzed to determine if they received any surgical intervention and, if so, which surgical subtype was used. Univariate analysis was then performed assessing patient length of survival for each surgical subtype. Data was analyzed using SPSS and statistical significance was set at α = 0.05. Results: A total of 2208 patients were included that had survival data and had received surgical intervention. The mean survival time of all patients was 118.1 months. Surgical patients survived an average of 137.2 months while nonsurgical patients survived 96.0 months on average (p &lt; .00001). Analysis of surgical subtypes revealed significantly longer survival in patients who underwent radical excision with limb salvage compared to patients who underwent partial resection (p &lt; .05). Patients who received a partial limb amputation survived significantly longer than patients who received a total limb amputation (p &lt; .01). Patients who underwent local tumor excision or radial excision with limb salvage also survived significantly longer than patients with total limb amputation (p &lt; .05 and p &lt; .01, respectively). Conclusions: This study found that receipt of surgery is associated with longer survival in Ewing sarcoma patients. Further, different surgical interventions may influence survival in Ewing sarcoma as patients receiving radical excision with limb salvage fared better than partial resection and partial limb amputation better than total limb amputation. Future studies would benefit from investigating additional variables that may influence receipt of surgical interventions including patient demographics, socioeconomic status, and surgical center type.[Table: see text]
Pan-Cancer analysis of the mutation frequency of genes in TGF-beta pathway.
Authors: Qiang Fu, Junyan Su
Journal: Journal of Clinical Oncology (2022)

e15113 Background: The TGF-β signaling pathway governs key cellular processes under physiologic conditions and deregulates in cancer, including a diverse and varied set of gene responses that range from cytostatic and apoptotic tumor-suppressive ones in early-stage tumors to proliferative, invasive, angiogenic, and oncogenic ones in advanced cancer. However, the genomics profiles of TGF-β signaling pathway genes are unclear. In this study, we evaluated the genomic features in Chinese pan-cancer patients and investigated the mutation frequency of genes in the TGF-β pathway. Methods: A total of 5420 patients consisting of 22 cancer types were enrolled in this study. Utilizing target next-generation sequencing (NGS) platform, genomic profiling of 599 cancer-related genes, including genes of TGF-β pathway (SMAD2/3/4, PDGFRB, CDH1, MDM2, CDKN1A, and CDKN2B), was performed on tumor tissue or blood samples. Results: We observed 25.57% (1386/5420) of cases harbored at least one alteration in the TGF-β pathway genes. The mutation frequency ranges 9.09% to 39.77% among the 22 cancer types, including 39.77% (247/621) in gastric cancer, 39.31 (320/814) in bowel cancer, 36.84% (7/19) in endometrial cancer, 11.11% (8/72) in esophageal cancer, 10.46% (7/67) in kidney cancer, and 9.09% (2/22) in the gastrointestinal stromal tumor, respectively. The mutation of tumor-promoting effects genes SMAD2/3/4, PDGFRB, CDH1and MDM2 in the TGF-β pathway were found in all cancer types and mainly occurred in CNS tumor, gastrointestinal stromal tumor, pancreatic cancer, sarcoma, gastric cancer, and bowel cancer. The tumor-suppressing effective genes CDKN1A and CDKN2B primarily mutated in melanoma, endometrial cancer, and kidney cancer. Approximately 21.77% of patients had CNV in the TGF-β pathway of all tumor types. The most frequently mutated TGF-β genes were MDM2 and CDKN2B, mainly altered in sarcoma, melanoma, and CNS Tumor. Conclusions: We found a unique genomic feature of the TGF-β pathway of Chinese pan-cancer patients. Targeting mutant of TGF-β pathway genes remains a potentially effective treatment in the future.
Synergistic effects of low-dose belantamab mafodotin in combination with a gamma-secretase inhibitor (nirogacestat) in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-5 study.
Authors: Sagar Lonial, Sebastian Grosicki, Marek Hus, Kevin W. Song, Thierry Facon, Natalie Scott Callander, Vincent Ribrag, Katarina Uttervall, Hang Quach, Vladimir I. Vorobyev, Chang Ki Min, Shinta Cheng, L. Mary Smith, Jing Yu, Therese Collingwood, Beata Holkova, Brandon Kremer, Ira Gupta, Paul G. Richardson, Monique C. Minnema
Journal: Journal of Clinical Oncology (2022)

8019 Background: Preclinical data demonstrate that nirogacestat, a gamma-secretase inhibitor, may increase cell-surface levels of a B-cell maturation antigen (BCMA) and reduce soluble BCMA levels, which could enhance anti-BCMA agent activity in multiple myeloma. In the DREAMM-5 (NCT04126200) Phase I/II platform trial belantamab mafodotin (belamaf; BLENREP), a BCMA-targeting antibody-drug conjugate, is being evaluated in combination with nirogacestat to determine if the combination can result in similar efficacy and an improved ocular safety profile compared to the currently approved belamaf schedule (single agent dose 2.5 mg/kg Q3W) in patients with RRMM which showed a 31% overall response rate (ORR) and 44.5% Gr3/4 keratopathy (BLENREP US prescribing information). Methods: This cohort within the DREAMM-5 nirogacestat combination sub-study has a sequential dose-exploration (DE) phase evaluating 0.95 mg/kg Q3W belamaf with 100 mg BID nirogacestat continuously, followed by a randomized cohort expansion (CE) comparing the combination to a belamaf 2.5 mg/kg Q3W arm. Results: Preliminary results from the 10 patients (pts) in the DE cohort with low-dose belamaf + nirogacestat are presented in this abstract. Pts had a median (range) of 4.5 (3–10) prior lines of therapy. At time of data cut-off (Nov 15, 2021), pts received a median (range) of 7 cycles (1–26). The ORR was 60% (n=6/10) and 20% (n=2) achieved a very good partial response (Table). The key emergent adverse events (AEs) included ocular events (n=7 [70%]; ≥Grade [Gr] 3, n=2 [20%] of which Gr 3 keratopathy was reported in 1 pt [10%]), diarrhea (n=7 [70%]; Gr 3, n=1 [10%]) and hypophosphatemia (n=7 [70%]; Gr 3, n=1, [10%]). There were 2 Grade 5 AEs, neither of which were related to study treatment. No pt permanently discontinued study due to treatment related AEs. Conclusions: Encouraging clinical activity and a manageable safety profile is observed with low dose belamaf (0.95 mg/kg Q3W) + nirogacestat (100 mg BID continuously) in pts with RRMM. This ongoing sub-study is actively recruiting patients and will continue to evaluate belamaf + nirogacestat efficacy and safety. Updated results will be reported at the congress. Funding: GSK (208887); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT04126200. [Table: see text]